This study explored Sapindus saponins role in the proliferation and metastasis of colorectal cancer cells and its possible mechanism. SW620 cells were divided into 8 groups; control group, Sapindus saponin-low group, Sapindus saponin-middle group, Sapindus saponin-high group, microRNA+negative control group, microRNA-5590-3p group, Sapindus saponin+anti-microRNA-negative control group and Sapindus saponin+anti-microRNA-5590-3p group. Cell proliferation and metastasis were determined using colony formation assay, wound healing assay, 3-(4,5-dimethylthiazol-2-yl)-2,5 diphenyl tetrazolium bromide assay and transwell assay. MicroRNA-5590-3p expression was detected by quantitative reverse transcription-polymerase chain reaction. Matrix metalloproteinases-2 and matrix metalloproteinases-9 protein levels were examined by Western blot. SW620 cell proliferation inhibition rate and microRNA-5590-3p expression were increased, while colony numbers, invaded cell numbers, wound healing rate, matrix metalloproteinases-2 and matrix metalloproteinases-9 protein levels were decreased in Sapindus saponin-low group, Sapindus saponin-middle group, Sapindus saponin-high group in a dose-dependent manner. Besides, microRNA-5590-3p overexpression increased SW620 cell proliferation inhibition rate, while suppressed colony numbers, invaded cell numbers, wound healing rate, matrix metalloproteinases-2 and matrix metalloproteinases-9 protein levels. Compared with the Sapindus saponin+anti-microRNA-negative control group, SW620 cell proliferation inhibition rate was reduced, while colony numbers, invaded cell numbers, wound healing rate, matrix metalloproteinases-2 and matrix metalloproteinases-9 protein levels were enhanced in the Sapindus saponin+anti-microRNA-5590-3p group. Sapindus saponin could repress colorectal cancer cell proliferation and metastasis by upregulating microRNA-5590-3p.